NDRG2 在阿尔茨海默病中的病理作用，一项使用动物模型和 APPwt 过表达细胞的研究。
The pathological roles of NDRG2 in Alzheimer's disease, a study using animal models and APPwt-overexpressed cells.
机构信息
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
出版信息
CNS Neurosci Ther. 2017 Aug;23(8):667-679. doi: 10.1111/cns.12716. Epub 2017 Jul 2.
Abstract
AIMS
To investigate the roles of N-myc downstream-regulated gene 2 (NDRG2) in the pathology of aging and neurodegenerative disease such as Alzheimer's disease (AD).
RESULTS
In this study, we confirmed the upregulation of NDRG2 in the brains of aging and AD animal models. To explore the role of NDRG2 in the pathology of AD at molecular level, we conducted a cell-based assay of highly expressed wild-type human APP695 SK-N-SH cells (SK-N-SH APPwt). By silencing and overexpressing gene of NDRG2, we demonstrated that NDRG2-mediated increase in Aβ was through the pathways of BACE1 and GGA3. NGRG2 improved tau phosphorylation via enhanced activity of CDK5 and decreased Pin1, but it was not affected by GSK3β pathway. NDRG2 might also induce cell apoptosis through the extrinsic (caspase 8) apoptotic pathway by interaction with STAT3.
CONCLUSION
Our study confirmed the upregulation of NDRG2 in AD animal models and demonstrated its important roles in AD pathology. NDRG2 might be a potential target for studying and treatment of AD.
摘要
目的
研究 N- 霉基下游调节基因 2（NDRG2）在衰老和神经退行性疾病（如阿尔茨海默病（AD））的病理学中的作用。
结果
在这项研究中，我们证实了 NDRG2 在衰老和 AD 动物模型中的上调。为了从分子水平探讨 NDRG2 在 AD 病理学中的作用，我们对高表达野生型人 APP695 SK-N-SH 细胞（SK-N-SH APPwt）进行了基于细胞的测定。通过沉默和过表达 NDRG2 基因，我们证明 NDRG2 介导的 Aβ 增加是通过 BACE1 和 GGA3 途径实现的。NGRG2 通过增强 CDK5 的活性和降低 Pin1 来改善 tau 磷酸化，但不受 GSK3β 途径的影响。NDRG2 还可能通过与 STAT3 相互作用，通过外在（半胱天冬酶 8）凋亡途径诱导细胞凋亡。
结论
我们的研究证实了 NDRG2 在 AD 动物模型中的上调，并证明了其在 AD 病理学中的重要作用。NDRG2 可能是研究和治疗 AD 的潜在靶点。
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